Genetically determined high activities of the TNF-alpha, IL23/IL17, and NFkB pathways were associated with increased risk of ankylosing spondylitis

et al. 2019

Endocrine Connections

Background Accumulating data have shown that interleukin-27 (IL27) polymorphisms are linked to the susceptibility of some autoimmune diseases. We assessed whether there was an association between three single-nucleotide polymorphisms (SNPs) of IL27 gene and autoimmune thyroid diseases (AITDs). Methods Three SNPs (rs153109, rs17855750 and rs181206) of IL27 gene were genotyped by Hi-SNP high-throughput genotyping in 843 patients with AITDs (516 Graves’ disease (GD) and 327 Hashimoto’s thyroiditis (HT)) and 677 healthy controls in Chinese Han population. Results Compared with controls, rs153109 displayed significant associations with GD in allele and genotype frequencies (P = 0.002 and P = 0.008, respectively) and rs17855750 displayed significant associations with HT in allele frequencies (P = 0.02), whereas no differences in genotype or allele frequencies were found between AITD patients and controls at rs181206. Conclusion Our study, for the first time, showed the significant association of the IL27 gene SNPs with AITD.

Section: Discussionmentioning

confidence: 99%

Association of single-nucleotide polymorphisms in the IL27 gene with autoimmune thyroid diseases

et al. 2019

Endocrine Connections

“…Of all the interleukins secreted by Th17 cells, IL-1 β , IL-17, and IL-26 are most specific to Th17 cell response [ 2 , 8 – 11 ]. NF- κ B signaling, one of the significant pathways of the inflammatory process, is found to be involved in the etiology of AS [ 12 ]. NF- κ B induces the expression of TNF- α , IL-1 β , and other proinflammatory cytokines [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Punicalagin Exerts Protective Effects against Ankylosing Spondylitis by Regulating NF-κB-TH17/JAK2/STAT3 Signaling and Oxidative Stress

Feng

Yang

BioMed Research International

et al. 2020

Background. Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by sacroiliitis and spinal rigidity of the axial joints. The role of oxidative stress and increased proinflammatory cytokines is well documented in AS pathogenesis. Punicalagin (2,3-hexahydroxydiphenoyl-gallagyl-D-glucose), an ellagitannin widely present in pomegranates, is found to exhibit potent anti-inflammatory, antiproliferative, and antioxidative effects. The present study was undertaken to investigate the effects of punicalagin in a rodent model of AS. Methods. BALB/c mice induced spondylitis were sacrificed 24 h after the last injection of proteoglycan extract. Histological scoring was done to assess the degree of the disease. The expression of JAK2/STAT3 proteins and proteins of the nuclear factor-κB (NF-κB) pathway was determined by immunoblotting. Serum levels of inflammatory mediators—TNF-α, IL-1β, IL-6, IL-17A, and IL-23—were assessed. Levels of lipid peroxidation and reactive oxygen species (ROS) were quantified. Antioxidant status as a measure of activities of antioxidant enzymes—catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD)—was determined. Results. Punicalagin effectively improved antioxidant status and decreased lipid peroxidation, ROS production, and serum levels of inflammatory mediators. NF-κB pathway and JAK2/STAT3 signaling were significantly (p<0.05) downregulated. Punicalagin effectively regulated the production of cytokines by the Th17 cells and the IL-17A/IL-23 axis. Conclusion. The observations suggest that punicalagin exerts a protective role in AS via reducing oxidative stress and regulating NF-κB/TH17/JAK2/STAT3 signal. Punicalagin thus could be explored further as a potent candidate compound in the treatment of AS.

“…The phosphorylated STAT dimers enter the nucleus and act on downstream target genes. IL-23R has been identified to associate with multiple diseases, including alopecia areata (rs10889677) and nephropathy (rs10805303) (Figure 3) (Safrany et al, 2011;Yu et al, 2012;Huang et al, 2016;Qin et al, 2016;Poomarimuthu et al, 2018;Sode et al, 2018;Zhong et al, 2018;Kramer et al, 2019;Loures et al, 2019;Ruyssen-Witrand et al, 2019;Tabatabaei-Panah et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

The Association Study of IL-23R Polymorphisms With Cerebral Palsy in Chinese Population

Fan

et al. 2020

Front. Neurosci.

Background: Cerebral palsy (CP) is a syndrome of non-progressive motor dysfunction caused by early brain development injury. Recent evidence has shown that immunological abnormalities are associated with an increased risk of CP.Methods: We recruited 782 children with CP as the case group and 770 healthy children as the control group. The association between IL-23R single nucleotide polymorphisms (SNPs; namely, rs10889657, rs6682925, rs1884444, rs17375018, rs1004819, rs11805303, and rs10889677) and CP was studied by using a case–control method and SHEsis online software. Subgroup analysis based on complications and clinical subtypes was also carried out.Results: There were differences in the allele and genotype frequencies between CP cases and controls at the rs11805303 and rs10889677 SNPs (Pallele = 0.014 and 0.048, respectively; Pgenotype = 0.023 and 0.008, respectively), and the difference in genotype frequency of rs10889677 remained significant after Bonferroni correction (Pgenotype = 0.048). Subgroup analysis revealed a more significant association of rs10889677 with CP accompanied by global developmental delay (Pgenotype = 0.024 after correction) and neonatal encephalopathy (Pgenotype = 0.024 after correction).Conclusion: The present results showed a significant association between IL-23R and CP, suggesting that IL-23R may play a potential role in CP pathogenesis.